What to do with a patient who has a normal Hemoglobin A1c (HbA1c) level of 5.5 but an elevated glucose level of 300 in their urinalysis (u/a)?

Approach to Discordant Urinalysis Glucose and Normal A1c

Repeat the urinalysis now with a simultaneous plasma glucose measurement to determine if the elevated urinary glucose represents true hyperglycemia or a renal glycosuria. 1

Understanding the Discordance

Your patient presents with a significant mismatch between laboratory findings that requires immediate clarification:

• A1c of 5.5% reflects normal average glucose control over the preceding 2-3 months, corresponding to a mean plasma glucose of approximately 111 mg/dL 1
• Urinalysis glucose of 300 mg/dL is markedly elevated and would typically suggest significant hyperglycemia
• This discordance indicates either:
  • Laboratory error in one or both tests
  • Renal glycosuria (glucose spillage at normal blood glucose levels)
  • Acute hyperglycemia not yet reflected in A1c
  • Conditions affecting A1c accuracy

Immediate Next Steps

Obtain simultaneous measurements now:

• Repeat urinalysis to rule out laboratory error or specimen contamination 1
• Measure plasma glucose (fasting or random) at the same time as the repeat urinalysis 1
• Compare the two values directly - if plasma glucose is normal (<140 mg/dL random or <100 mg/dL fasting) but urinary glucose remains elevated, this confirms renal glycosuria 1

Diagnostic Algorithm Based on Results

If plasma glucose is ≥200 mg/dL with symptoms of hyperglycemia:

• Diabetes diagnosis is confirmed regardless of A1c 1
• The normal A1c may reflect rapidly evolving diabetes (such as developing type 1 diabetes) where A1c has not yet risen significantly 1
• Consider checking autoantibodies (GAD, IA-2, ZnT8) and C-peptide if type 1 diabetes is suspected 1

If plasma glucose is 126-199 mg/dL (fasting ≥126 mg/dL):

• Repeat fasting plasma glucose or perform oral glucose tolerance test for confirmation 1
• The discordance between A1c and glucose criteria should prompt repeat testing of the abnormal test 1
• Consider conditions affecting A1c accuracy (hemoglobinopathies, anemia, recent blood loss) 1

If plasma glucose is normal (<126 mg/dL fasting or <140 mg/dL random):

• Diagnosis is renal glycosuria - a benign condition where the renal threshold for glucose reabsorption is lowered 1
• No diabetes treatment is needed
• Document this finding to avoid future confusion
• Consider follow-up A1c testing in 3 years per standard screening guidelines 1

Critical Pitfalls to Avoid

Do not diagnose diabetes based on urinalysis glucose alone - urinary glucose is not a diagnostic criterion for diabetes and can be falsely elevated due to renal glycosuria, medications, or pregnancy 1

Do not ignore the possibility of A1c interference - conditions with abnormal red cell turnover (hemolytic anemia, iron deficiency anemia, recent blood loss, pregnancy) can falsely lower A1c 1. If suspected, use only glucose criteria for diagnosis 1

Do not delay confirmation testing - in the absence of unequivocal hyperglycemia with classic symptoms, all abnormal glucose tests should be confirmed by repeat testing before making a diabetes diagnosis 1

Ensure A1c was performed in a certified laboratory - point-of-care A1c assays are not recommended for diagnostic purposes due to lack of mandated proficiency testing 1

Follow-up Recommendations

• If all testing confirms normal glucose metabolism, reassure the patient and continue routine diabetes screening every 3 years (or more frequently if risk factors develop) 1
• If diabetes is confirmed, initiate appropriate treatment and education immediately 1
• Document the discordance and resolution in the medical record to guide future providers 1